Role of Glutathione-S-Transferase M1 (GSTM1) and T1 (GSTT1) Genes on Aluminum Concentration and Oxidative Markers among Autistic Children

Abstract

Autism Spectrum Disorder (ASD) is considered a multifaceted neurodevelopmental disorder. The last two decades showed an increase in its prevalence until reached about 1 in 54 children. Autistic symptoms may be exacerbated when the interaction of the genetic and the environmental risk factors occur, suggesting that gene-environment interaction could be a mechanism underlying the etiology of ASD. Aluminum is a known neurotoxic metal that has known health effects in humans. Glutathione-S-transferase (GST) genes and their enzymes play a major role in the detoxification of many toxic metals.Data were collected from 76 children aged 2-8 years diagnosed with ASD and 30 sex and age matched healthy children. The aim of this study was to investigate the association of polymorphisms in the two GST genes (GSTM1 and GSTT1) with mean aluminum concentrations (as, gene-environment interaction) and oxidative status markers (GST enzyme, malondialdehyde and nitric oxide) among the studied groups. The study started at December 2019 and last for one year at the clinics of National Research Centre, Egypt.The results of this study showed that the null GSTM1 and GSTT1 genotype is the most common type in ASD and that genotype may predispose ASD children to decreased antioxidant status (GST enzyme activity) which in term lead to mal detoxification of aluminum. There is marked increase in aluminum concentrations in hair of ASD children and oxidative markers (increase in MDA and NO) leading to oxidative damage that may play an important role in children autistic status. The study recommends adding antioxidant supplements to daily diet of ASD children to improve their antioxidant status and in term improving management of patients with autism spectrum disorders. Further studies are needed to describe other GST gene polymorphisms.